Tissue and Blood Biomarkers in Lung Cancer: A Review

Adv Clin Chem. 2018:86:1-21. doi: 10.1016/bs.acc.2018.05.001. Epub 2018 May 30.


Lung cancer is the most common cause of cancer-related death, worldwide. Historically, lung cancer has been divided into two main histological types: small cell and nonsmall cell (NSC) type with the latter being subdivided into adenocarcinoma, squamous cell type, and large cell type. The treatment of the NSC lung cancer (NSCLC), especially the adenocarcinoma subtype, has been transformed in the last decade by the availability of predictive biomarkers for molecularly targeted therapies. Currently, for patients with advanced adenocarcinomas, testing for sensitizing mutations in epidermal growth factor receptor (EGFR) is mandatory prior to the administration of anti-EGFR inhibitors such as erlotinib, gefitinib, afatinib, or osimertinib. For patients unable to provide tumor tissue, EGFR mutational analysis may be performed on plasma. For predicting response to crizotinib, testing for ALK and ROS1 gene rearrangement is necessary. The presence of ALK rearrangements is also a prerequisite for treatment with ceritinib, alectinib, or brigatinib. For predicting response to single agent pembrolizumab in the first-line treatment of patients with advanced adenocarcinoma or squamous cell NSCLCs, PD-L1 should be measured by an approved assay (e.g., PD-L1 IHC 22C3 pharmDx method). Although not widely used, serum biomarkers such as neuron-specific enolase, progastrin-releasing peptide, carcinoembryonic antigen, CYFRA 21-1, and squamous cell carcinoma antigen may help in the differential diagnosis of lung cancer when a tissue diagnosis is not possible. Serum biomarkers may also be of use in determining prognosis and monitoring response to systemic therapies. With the increasing use of biomarkers, personalized treatment especially for patients with adenocarcinoma-type NSCLC is finally on the horizon.

Keywords: ALK; Biomarkers; EGFR; Lung cancer; ROS; Serum; Tissue.

Publication types

  • Review

MeSH terms

  • Anaplastic Lymphoma Kinase / genetics
  • Animals
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Biomarkers, Tumor / analysis
  • Biomarkers, Tumor / blood
  • Biomarkers, Tumor / genetics
  • ErbB Receptors / genetics
  • Gene Rearrangement
  • Humans
  • Lung / drug effects
  • Lung / metabolism
  • Lung / pathology*
  • Lung Neoplasms / blood*
  • Lung Neoplasms / diagnosis*
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / genetics
  • Mutation
  • Prognosis


  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Anaplastic Lymphoma Kinase
  • EGFR protein, human
  • ErbB Receptors